TY - JOUR
T1 - Exploring the Reactivity and Biological Effects of Heteroleptic N-Heterocyclic Carbene Gold(I)-Alkynyl Complexes
AU - Oberkofler, Jens
AU - Aikman, Brech
AU - Bonsignore, Riccardo
AU - Pöthig, Alexander
AU - Platts, James
AU - Casini, Angela
AU - Kühn, Fritz E.
N1 - Publisher Copyright:
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
PY - 2020/3/27
Y1 - 2020/3/27
N2 - With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic AuI complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3-dihydroimidazolylidene) were synthesized and characterized by 1H and 13C NMR and elemental analysis, and in some cases also by X-ray diffraction. The compounds were all stable in H2O/DMSO as established by NMR spectroscopy, while they could react with model thiols (EtSH) in the presence of water to undergo ligand-substitution reactions. 1H NMR experiments showed that dissociation of the more labile alkynyl ligand was possible for all compounds, while in the case of the benzimidazolylidene series also dissociation of the NHC ligand could be observed. DFT calculations suggest that, depending on the steric hindrance exerted by both the NHC wingtip groups and the alkynyl substituents, the reaction can proceed either via a π-stabilized intermediate or with the alkynyl ligand remaining purely σ-coordinated to the AuI center until completely dissociated. The most stable compounds in PBS buffer (pH 7.4), as assessed by UV-Visible spectrophotometry, were further investigated for their ability to stabilize G4 DNA by FRET DNA melting assay, showing only moderate activity. Moreover, two derivatives were tested in vitro for their anticancer activities in three different human cancer cell lines and showed cytotoxicity in the low micromolar range.
AB - With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic AuI complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3-dihydroimidazolylidene) were synthesized and characterized by 1H and 13C NMR and elemental analysis, and in some cases also by X-ray diffraction. The compounds were all stable in H2O/DMSO as established by NMR spectroscopy, while they could react with model thiols (EtSH) in the presence of water to undergo ligand-substitution reactions. 1H NMR experiments showed that dissociation of the more labile alkynyl ligand was possible for all compounds, while in the case of the benzimidazolylidene series also dissociation of the NHC ligand could be observed. DFT calculations suggest that, depending on the steric hindrance exerted by both the NHC wingtip groups and the alkynyl substituents, the reaction can proceed either via a π-stabilized intermediate or with the alkynyl ligand remaining purely σ-coordinated to the AuI center until completely dissociated. The most stable compounds in PBS buffer (pH 7.4), as assessed by UV-Visible spectrophotometry, were further investigated for their ability to stabilize G4 DNA by FRET DNA melting assay, showing only moderate activity. Moreover, two derivatives were tested in vitro for their anticancer activities in three different human cancer cell lines and showed cytotoxicity in the low micromolar range.
KW - Alkyne ligands
KW - Antitumor agents
KW - G-quadruplexes
KW - Gold
KW - N-heterocyclic carbenes
KW - Thiols
UR - http://www.scopus.com/inward/record.url?scp=85077883721&partnerID=8YFLogxK
U2 - 10.1002/ejic.201901043
DO - 10.1002/ejic.201901043
M3 - Article
AN - SCOPUS:85077883721
SN - 1434-1948
VL - 2020
SP - 1040
EP - 1051
JO - European Journal of Inorganic Chemistry
JF - European Journal of Inorganic Chemistry
IS - 11-12
ER -